Angiogenesis in vivo occurs during normal wound healing and during the vascularization of solid tumors. It is a complex process involving degradation of the basement membrane, the migration and proliferation of endothelial cells, and tube formation. Several factors have been shown to stimulate angiogenesis, including FGF, vascular endothelial growth factor (VEGF), transforming growth factor o: (TGF-Ot), angiogenin, transforming growth factor-^ (TGF-f-'), TNF-tt,10^ and insulin-like growth factor 1 (IGF-l).i04 Their properties are summarized in Table 6-3. Some of these factors stimulate angiogenesis by inducing endothelial cell migration and proliferation (FGF and VEGF); others appear to do so by stimulating endothelial cell differentiation (TGF-ft and TNF-'I) or by activating a secondary cell type to produce angiogenic factors (angiogenin, TGF-ft, and TNF-g). Angiogenesis may be negatively regulated by both naturally occurring and synthetic compounds. It can be inhibited by the combination of heparin and cortisone,105 thrombospondin, platelet factor IV, and g-interferon. Many of these agents bind to heparin, suggesting that they exert their growth-inhibitory effects by blocking the action of heparin-binding growth factors, such as FGF. It is likely that the control of angiogenesis rests on the maintenance of a balance between the stimulatory and inhibitory factors, the regulation of which is not yet fully understood.
Table 6-3: Angiogenic Stimulators and Inhibitors
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